Interleukin-10 (IL-10), also known as cytokine synthesis inhibitory factor (CSIF), is normally expressed in T cells, macrophages, monocytes, dendritic cells, mast cells, B cells, eosinophils, keratinocytes, epithelial cells, and various tumor cell lines (reviewed by Williams et al. (2004) Immunology 113:281-92). IL-10 has anti-inflammatory properties that may be exploited for the treatment of a number of illnesses. IL-10 is naturally synthesized in the CNS and acts to limit clinical symptoms of stroke, multiple sclerosis, Alzheimer's, and meningitis. In particular, IL-10 induces anergy in brain-infiltrating T cells by inhibiting cell signaling through CD28-CD80/86 costimulation and promotes survival of neurons and glial cells by blocking proapoptotic cytokines. Strle et al. (2001) Crit. Rev. Immunol. 21:427-49. Further discussion of the use of IL-10 for the treatment of neuropathic pain can be found in Milligan et al. (2005) Molecular Pain 1:9. IL-10 has also been proposed as therapy for a number of other diseases for which anti-inflammatory activity is predicted to be beneficial.
Despite these advantageous anti-inflammatory properties, IL-10 elicits side effects that have limited its clinical development. For example, the cell proliferative activity of IL-10 is often undesirable, particularly when considering systemic administration.
Thus, there remains a need for new therapeutic approaches for treating neuropathic pain, neurological disorders and other inflammatory disorders that do not have the adverse side effects associated with administration of wild-type IL-10.